Should Clinicians Rethink Rectal Cancer Treatment for Younger Patients?

Early‐onset rectal cancer may differ biologically and in its response to multimodality therapy, according to a large retrospective study of NCCN data.

Rectal cancer patients under the age of 50 may not benefit from currently recommended therapy because those treatments are based on outcomes data from a much older cohort, according to a retrospective study published in CANCER, a peer-reviewed journal of the American Cancer Society. Atif Iqbal, MD, from the University of Florida College of Medicine, Gainesville, and coauthors report that rectal cancer patients younger than 50 years lacked a survival benefit from National Comprehensive Cancer Network (NCCN) guideline-directed treatment for stage II and III disease.

Early-onset disease, Iqbal et al theorize, may differ biologically and therefore may respond differently to multimodality therapy, compared with rectal tumors that present in older patients. The overall incidence of rectal cancer is decreasing in patients older than 50 years, likely as a result of improved screening adherence, they wrote. However, they emphasized, there is a disproportionate increase in rectal cancer incidence among patients under the age of 50. In addition, the mortality rate from rectal cancer among younger patients has increased over the past several decades.

Current national guidelines recommend a combination of chemotherapy, radiation, and surgery for stage II and III rectal cancer. However, the guidelines are predominantly based on data from patients older than 50. To examine how younger patients fare, Iqbal and colleagues evaluated 2004–2014 data from the NCCN.

The team analyzed data on 52,519 patients, and found patients younger than 50 years old who have been diagnosed with rectal cancer represent a unique group. These younger patients (who were more likely to be female and minorities) do not experience a survival benefit from receiving the currently recommended treatment for stage II and III rectal cancer. Patients younger than age 50 were also diagnosed at a higher stage. Younger patients were more likely to receive radiation outside NCCN guidelines for stage I rectal cancer. Iqbal said he hopes these findings will stimulate future research focused on younger patients with rectal cancer. 

Iqbal commented that these data may help to better inform physicians in their discussions with rectal cancer patients under the age of 50. Furthermore, he said studies are needed to evaluate how factors such as diet, physical activity, obesity, underlying genetics, and gut microbes may interact with rectal cancer biology.

Commenting on the study, Andrea (Andi) Dwyer, from the University of Colorado Cancer Center and the Director of Health Promotion for Fight Colorectal Cancer, Denver, said there are different schools of thought regarding whether there truly are biological differences between rectal cancer patients under age 50 vs over age 50.

Dwyer pointed out that interpretation of the findings is limited by the fact that this is a retrospective study. The current study also did not look at other clinically important endpoints for rectal cancer patients, such as local recurrence and disease-free survival (DFS). “I think there are other types of studies that have been done, and they showed that it looked like there might not be such a biological difference,” Dwyer told Cancer Network. “We think prospective studies are needed.”